Anthrax Lethal Factor Activates K+ Channels To Induce IL-1β Secretion in Macrophages

摘要: Anthrax lethal toxin (LeTx) is a virulence factor of Bacilillus anthracis that bivalent toxin, containing (LF) and protective Ag proteins, which causes cytotoxicity altered macrophage function. LeTx exposure results in early K+ efflux from macrophages associated with caspase-1 activation increased IL-1β release. The mechanism this toxin-induced unknown. goals the current study were to determine whether LeTx-induced mediated by effects on specific channels K+-channel activity involved Exposure induced significant increase activities two types have been identified mouse macrophages: Ba2+-sensitive inwardly rectifying (Kir) 4-aminopyridine–sensitive outwardly voltage-gated (Kv) channels. enhancement both Kir Kv required proteolytic LF, because mutant LF-protein (LFE687C) combined protein had no effect currents. Furthermore, blocking significantly decreased release IL-1β. In addition, retroviral transduction wild-type enhanced IL-1β, whereas dominant-negative blocked Activation was not for either These data indicate major through stimulates involves an LF-protease enhances channel function during stimulation.